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Stimulation strength controls the rate of initiation but not the molecular organisation of TCR-induced signalling

Published version
Peer-reviewed

Change log

Abstract

Millions of naïve T cells with different TCRs may interact with a peptide-MHC ligand, but very few will activate. Remarkably, this fine control is orchestrated using a limited set of intracellular machinery. It remains unclear whether changes in stimulation strength alter the programme of signalling events leading to T cell activation. Using mass cytometry to simultaneously measure multiple signalling pathways during activation of murine CD8+ T cells, we found a programme of distal signalling events that is shared, regardless of the strength of TCR stimulation. Moreover, the relationship between transcription of early response genes Nr4a1 and Irf8 and activation of the ribosomal protein S6 is also conserved across stimuli. Instead, we found that stimulation strength dictates the rate with which cells initiate signalling through this network. These data suggest that TCR-induced signalling results in a coordinated activation program, modulated in rate but not organization by stimulation strength.

Description

Funder: European Molecular Biology Organization; FundRef: http://dx.doi.org/10.13039/100004410

Keywords

Research Article, Computational and Systems Biology, Immunology and Inflammation, T cell receptor, signalling, CD8 T cells, mass cytometry, Mouse

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X

Volume Title

9

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Wellcome (103930)
Wellcome (100140)
Wellcome (217100)
Wellcome (204017/Z/16/Z)
Cancer Research UK (A17197)
Medical Research Council (MR/P014178/1)
Addenbrooke's Charitable Trust, Cambridge University Hospitals (23/17 A (ii))